Final Report Summary - INTRASPACE (An intracellular approach to spatial coding in the hippocampus)
In a first part of the project we wanted to see whether a specific level of intrinsic excitability is permanently attached to a given cell or whether a regulatory mechanism might exist. This question was motivated by observation that cells ensembles vary between different environments. In vitro studies had described long-term plasticity of intrinsic excitability in the hippocampus but we did not whether these mechanisms might be observed in the intact brain in vivo. Using stimulations applied via the patch-pipette we were able to induce a fast and long-lasting decrease in excitability and investigate some induction and expression mechanisms. We propose that this mechanism will prevent the same cells from always being activated thus reducing memory interference. Along the same line we wanted to see if the link between intrinsic excitability and allocation is still observed when animal explore a familiar environment. We thus used intracellular recordings to probe input/ouput function of CA1 pyramidal cells as mice explore virtual reality environment. We observe that cells with a high level of excitability tend to get hyperpolarized during movement suggesting that they are not involved in coding during spatial navigation. This result support our hypothesis of a switch from intrinsic to synaptic mechanisms of place cells activation with familiarization of an environment. This result was further confirmed using two-photon calcium imaging in navigating animals (in collbaoration with the Cossart lab).
In a second part of the project we wanted to see whether the recruitment rule based on intrinsic excitability differed in other part of the hippocampal formation and we started to correlate the level of intrinsic excitability and the recruitment probability of cells in upstream parts of the hippocampal formation.
In a third and last part of the project we wanted to understand the mechanisms behind changes in the coding of place cells that are observed when changes occur in a familiar environment, which is closer to our everyday experience. We often take the same streets to go from home to work but the parked cars have changed, the people in the street are different, the trees have lost their leaves during winter yet we can always find our way. For this we made use of virtual reality to be able to modify instantaneously and in a controlled way the explored environments. The use of virtual reality allowed us to reveal the importance of proximal visual landmarks for the accurate coding of space. We also found that modulating these landmarks could profoundly modify the coding of a familiar environment a process called remapping. The intracellular mechanisms behind these changes were investigated with whole-cell patch clamp recordings.
Overall this project aims at revealing the cellular mechanisms involved in the formation of spatial memories, which allow us to navigate. This essential function is impaired in several neurological diseases such as Alzheimer disease and temporal lobe epilepsy.